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Imir Tekneci, Zeynep (2025) Microfluidic Production of Cell Instructive Microparticles in Wound Healing. PhD thesis, University of Nottingham.

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Abstract

Protein adsorption is considered to be the primary reaction when a biomaterial comes into contact with any biological medium and cells react to the proteins present in this bio-interface. As the adsorbed protein type and capability are determined by the chemical and physical structures of implanted biomaterials, biomaterial chemistry influences cell behaviour. The foreign body response is a challenging phenomenon that may result in serious health issues for patients after implantation. Conditions such as diabetic wounds, burn injuries, or medical implants can cause impaired control of the wound-healing process that may lead to chronic wounds and/or fibrosis. The discovery of cell-instructive materials offers an excellent opportunity for modulating immune cell response to achieve increased implant acceptance and accelerate the healing of chronic wounds. The advancement of bio-functional biodegradable materials has become increasingly significant due to their successful applications without causing any accumulation or adverse reactions of byproducts in the body post-treatment. Thus, this study aimed to develop cell-instructive polymer microparticles with biodegradable cores to improve wound healing. The biointerface with the materials was investigated using mass spectrometry.

Immune instructive polymers were identified in previous work using high throughput in vitro screening and in vivo validation. Here, surface-decorated microparticles were produced using synthesised cell-instructive surfactants in a microfluidic system. The effect of anti and pro-inflammatory microparticles on macrophage polarisation was investigated. Proliferative microparticles with a biodegradable core were utilised in fibroblast cell culture and in an in vitro wound healing model. It was observed that these microparticles supported fibroblast proliferation and modulated secreted cytokine profile and accelerated in vitro wound healing. Also it was observed that microparticles promoted cell attachment by serving as a bridge between elongated. To gain insight into the mechanism at the cell-biomaterial interface, protein and lipid adsorption on microparticle surfaces from serum-supplemented culture medium was investigated. It was observed that microparticles had varying protein and lipid depositions depending on their surface chemistry, resulting in having a biologically distinct identity.

In summary, findings from this study demonstrate the potential of surface-decorated biodegradable microparticles to modulate fibroblast phenotype and behaviour. Also, the possible impact of protein and lipid deposition on the surface of microparticles on wound healing mechanisms is highlighted. These observations may provide an approach to facilitating the advancement of biodegradable microparticles with bio-instructive surface chemistry, with future applications in wound healing.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Alexander, Morgan R. Ghaemmaghami, Amir M. Irvine, Derek J. Dundas, Adam A.
Keywords:	polymer microparticles, biomaterials, wound healing
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General) > R855 Medical technology. Biomedical engineering. Electronics
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	80461
Depositing User:	IMIR, ZEYNEP
Date Deposited:	10 Apr 2025 09:53
Last Modified:	10 Apr 2025 09:53
URI:	https://eprints.nottingham.ac.uk/id/eprint/80461

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